Multiple Myeloma

Multiple myeloma (MM) is a malignant proliferation of clonal bone marrow plasma cells (BMPCs) characterized by a clinically and genetically complex landscape. This cancer accounts for approximately 2% of all cancers and 10% of all hematological malignancies. Despite the remarkable improvement in treatment and patient care, MM remains an incurable disease. MM presents a profound genomic instability that also affects the non-coding genome, leading to lncRNA expression de-regulation which adds a further layer of complexity to the pathobiology of the disease. However, there is still a gap of knowledge concerning the exact lncRNAs mechanism of action and therapeutic potential in MM scenario, therefore clarifying their role may be of relevance.

Investigation of NEAT1 role in MM

Noemi Puccio, Gloria Manzotti, Christian Boni

NEAT1 is a lncRNA representing the essential architectural scaffold of nuclear paraspeckles organelles biogenesis and assembly. We have shown that the lncRNA NEAT1 is overexpressed in MM patients and demonstrated that NEAT1 supports the proliferation and the viability of MM cells both in vitro and in vivo, regulating the activity of DNA repair processes. Recently, we confirmed the pivotal role of NEAT1 in the maintenance of genome integrity by supporting the acquisition of a pro-survival and pro-oncogenic phenotype of MM cells cultured under non-physiological condition. Based on this important evidence, our project aims to identify the molecular mechanisms that drive the pro-tumoral function of NEAT1 and its potential druggability in MM.

Discovery of novel lncRNAs deregulated in MM patients harboring DIS3 gene alterations

Noemi Puccio, Gloria Manzotti, Christian Boni

DIS3 is a multi-domain protein that provides the catalytic activity of exosome, a complex involved in RNA degradation and metabolism. Alterations in the DIS3 locus were reported in 50 % of MM patients and correlated with reduced survival probability. These alterations are associated with the impairment of the RNA exosome function leading to a profound rewiring of the lncRNA program. Due to the clinical relevance of DIS3 in MM and the biological implications related with lncRNAs de-regulation, the proposal of our project is to characterize the function of the DIS3-associated lncRNAs to shed light on their contribution to MM pathobiology.